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MICROBIAL PATHOGENESIS · 2024 · IF 3.3

Regulation of lactate accumulation in bovine mammary epithelial cells by LPS-induced HIF-1α/MCT1 pathway

Xiaoye Cheng,Yijin Jiang,Xu Zhao,Nana Ma,Xiangzhen Shen

Lactate has been increasingly recognized for its role in diseases progression, necessitating a deeper understanding of its metabolic processes and regulatory mechanisms. This study aimed to evaluate the impact of lipopolysaccharide (LPS) on lactate accumulation in bovine mammary epithelial cells (BMECs) and to elucidate the underlying regulatory mechanisms. Further optimization of LPS treatment points was achieved by assessing the content of key glycolytic enzymes-hexokinases (HK), pyruvate kinase (PK) and pyruvate dehydrogenase (PDH)-as well as the expression levels of HK2, pyruvate dehydrogenase kinase4 (PDK4) and lactate dehydrogenase (LDHA). Our results indicate that LPS can promote intracellular glycolysis and inhibits pyruvate synthesis, thereby increasing lactate content. BMECs were cultured and divided into a control group (CON) and an LPS-stimulated group (10 μg/mL for 6 h, LPS group). LPS was found to upregulate expression levels of HIF-1α and MCT1, suggesting a role for HIF-1α and MCT1 in cellular glucose metabolism. To explore the effect of HIF-1α on lactate accumulation, BMECs were stimulated with a HIF-1α inducer (COCL 2 ) and HIF-1α inhibitor (DMBPA). COCL 2 was observed to promote lactate accumulation, while DMBPA inhibited it. Additionally, modulation of HIF-1α expression influenced the expression of MCT1, which is a crucial transporter for extracellular lactate influx. To investigate the specific impact of MCT1 on intracellular lactate, we utilized overexpression plasmids and small interfering RNA to modulate MCT1 expression. The findings indicate that while MCT1 expression alone does not affect intracellular lactate levels, it does modulate the changes induced by LPS. In conclusion, our study suggests that LPS regulates lactate accumulation in BMECs through the HIF-1α/MCT1 pathway, providing insights into the metabolic dysregulation associated with LPS-induced stress in dairy cattle.

CAS / MDL: 7646-79-9 1568-83-8
研究领域: 动物科学 · 细胞生物学 · 代谢学 · 乳品科学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2023 · IF 4.2

Synergistic Production of Pyruvic Acid and Propionic Acid over Defect-Rich MoS2

Yiyun Wang,Xinli Li,Zhi Chen,Kai Ma,Congming Tang

This work reported the coupling reaction of lactic acid (LA) to produce pyruvic acid (PyA) and propionic acid (PA) simultaneously over defect-rich MoS2 nanosheets. The process intensification linked to dehydrogenation of LA and hydrodeoxygenation of LA brings about the advantage that is not supplied additionally with oxygen and hydrogen, achieving a green and safe route. The defected structure is characterized by high-resolution transmission electron microscopy (HRTEM) and positron annihilation lifetime spectroscopy (PALS), which promotes the catalytic performance for the coupling reaction of LA. To fully understand the importance of the defected structure, the catalytic performance of defect-free MoS2 is also evaluated. It is found that the PyA/PA ratio is less than 1 and acetaldehyde selectivity is relatively high, suggesting that the produced hydrogen from the dehydrogenation of LA is insufficient for hydrodeoxygenation of LA over defect-free MoS2, and the difference of hydrogen comes from the side reactions of decarbonylation and decarboxylation of LA. Unlike the defect-free MoS2, the dehydrogenation of LA over the defect-rich MoS2 can provide sufficient hydrogen for hydrodeoxygenation of LA, so that the side reactions are drastically weakened. The widened interplanar spacing can fully expose the defect and the LA reactant molecule is more accessible to defective sites, which can endow a better catalytic activity. Surface hydrophilicity can improve adsorption and transfer, and better activity is observed over the defect-rich MoS2 and widened defect-rich MoS2. At 300 °C and a LA LHSV of 2.6 h–1 under an inert atmosphere, the catalyst offers a satisfactory total selectivity to pyruvic acid and propionic acid of about 85%, and the molar ratio of pyruvic acid/propionic acid is 1.1.

研究领域: 化学工程 · 催化科学
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ANNALS OF CLINICAL AND LABORATORY SCIENCE · 2017 ·Vol. 47 ·期 6 ·676-686 · IF 0.727

Enzyme Kinetic Assay to Measure the Activity of Tumor M2 Pyruvate Kinase in Breast Cancer Patients

Mingxiu Guan,Yingna Tong,Xiaobin Liu,Dong Dong,Yunli Zhou

Background M2 type Pyruvate kinase (PKM2) is the key rate-limiting enzyme of glycolysis, and it mainly exists as a dimer in tumor cells.This study aims to establish an enzyme kinetic assay for serum tumor M2 pyruvate kinase (TuM2-PK), and to evaluate its diagnosticvalue in breast cancer. Methods The catalytic kinetics of Pyruvate Kinase (PK) was examined. Its allosteric regulation property and Michaelis constant werethen measured. Next, the levels of TuM2-PK in serum were detected and compared with results from an enzyme-linked immunosorbentassay (ELISA). Finally, the levels of TuM2-PK among breast cancer patients, post-mastectomy patients, patients with benignbreast diseases, and healthy controls were compared. Results A PK kinetic assay was established in this study. The assay reaction time is 108 seconds, and the optimum pH level is 8.0.In the presence of the allosteric activator fructose 1, 6-bisphosphate (FBP), the Km of PK for phosphoenolpyruvate (PEP) is0.15 mmol/L and the Vmax is 330 μmol/min. The levels of TuM2-PK in serum obtained by enzyme kinetics are comparable to theELISA results. Both assays showed that TuM2-PK in breast cancer patients was increased from stage I to IV. Importantly, TuM2-PKlevels were significantly different between early and late-stage breast cancer patients (stage I and stage II vs. stage IIIand IV), as well as between late-stage and non-malignant patients (p<0.05). No statistical difference was found between benign breast disease patients and healthy controls. Conclusions An enzyme kinetic assay of serum TuM2-PK was successfully established and may be useful for breast cancer diagnosis.

CAS / MDL: 38099-82-0
研究领域: 肿瘤学 · 生物化学 · 癌症诊断 · 酶学
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EBioMedicine · 2018 · IF 6.183

Berberine Reduces Pyruvate-driven Hepatic Glucose Production by Limiting Mitochondrial Import of Pyruvate through Mitochondrial Pyruvate Carrier 1

Aiyun Li,Qun Liu,Qiang Li,Baolin Liu,Yang Yang,Ning Zhang

Background Mitochondrial pyruvate import via mitochondrial pyruvate carrier (MPC) is a central step in hepatic gluconeogenesis. Berberine inhibits hepatic gluconeogenesis, but the mechanism is incompletely understood. This study aims to investigate whether berberine could reduce excessive hepatic glucose production (HGP) by limiting mitochondrial import of pyruvate through MPC1. Methods High-fat diet (HFD) feeding augmented HGP. The effects of berberine on hepatic fatty acid oxidation, sirtuin3 (SIRT3) induction and mitochondrial pyruvate carrier 1 (MPC1) function were examined. Findings HFD feeding increased hepatic acetyl coenzyme A (acetyl CoA) accumulation with impaired pyruvate dehydrogenase (PDH) activity and increased pyruvate carboxylase (PC) induction. Berberine reduced acetyl CoA accumulation by limiting fatty acid oxidation and prevented mitochondrial pyruvate shift from oxidation to gluconeogenesis through carboxylation. Upon pyruvate response, SIRT3 binded to MPC1 and stabilized MPC1 protein via deacetylation modification, facilitating mitochondrial import of pyruvate. Berberine preserved the acetylation of MPC1 by suppression of SIRT3 induction and impaired MPC1 protein stabilization via protein degradation, resultantly limiting mitochondrial pyruvate supply for gluconeogenesis. Interpretation Berberine reduced acetyl CoA contents by limiting fatty acid oxidation and increased MPC1 degradation via preserving acetylation, thereby restraining HGP by blocking mitochondrial import of pyruvate. These findings suggest that limitation of mitochondrial pyruvate import might be a therapeutic strategy to prevent excessive hepatic glucose production.

研究领域: 药理学 · 代谢学 · 肝病学 · 分子生物学
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Inorganic Chemistry Frontiers · 2023 ·Vol. 10 ·期 15 ·4562-4568 · IF 7

Photoreforming of polyester plastics into added-value chemicals coupled with H2 evolution over a Ni2P/ZnIn2S4 catalyst

Chu-Xuan Liu,Rui Shi,Wangjing Ma,Fulai Liu,Yong Chen

The recycling of plastic waste has attracted increasing attention because of its negative effects on the ecological environment and human health. Photoreforming is emerging as a green and promising approach for upcycling plastic waste into highly valuable chemicals and H2 fuels. Herein, an earth-abundant Ni2P/ZnIn2S4 catalyst prepared by mechanical grinding is reported to selectively photoreform various polyester plastics into high-added-value chemicals coupled with H2 evolution under mild conditions. In particular, polylactic acid (PLA) can be upcycled to pyruvic acid (PA) with high activity (745.9 μmol g−1 h−1) and selectivity (>90%). Moreover, the H2 evolution rate can reach up to 781.3 μmol g−1 h−1 catalyzed by 7.5 wt% Ni2P/ZnIn2S4. This system exhibits excellent photocatalytic performance, benefiting from efficient photogenerated charge carrier separation and transfer between Ni2P and ZnIn2S4. This study provides a viable and promising solution for simultaneously producing high-purity H2 and added-value chemicals from polyester plastic waste, demonstrating its potential for practical recycling applications.

CAS / MDL: 7681-53-0
研究领域: 环境科学 · 材料科学 · 化学工程
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SEPARATION AND PURIFICATION TECHNOLOGY · 2020 · IF 5.774

Salting-out extraction of acetoin from fermentation broths using hydroxylammonium ionic liquids as extractants

Yan Li,Jian-Ying Dai,Zhi-Long Xiu

The salting-out extraction (SOE) systems based on ionic liquids (ILs) have attracted extensive attention in the separation of bio-based products, in which imidazolium ILs were widely studied. However, the high cost and toxicity have hindered their further industrial application. Hydroxylammonium ILs have the characteristics of cheap raw material, simple synthesis process and low toxicity, but are rarely used in the SOE systems. In this work, five hydroxylammonium ILs (2 cations and 4 carboxylate anions) were synthesized and used in SOE of bio-chemicals. The phase forming abilities of ILs with K 3 PO 4 and H 2 O were affected by the hydrophilicity of anions and cations. With the increase of carbon chain length, phase forming abilities of ILs increased, while the temperature had little influence. The partition behaviors of acetoin, ILs and 2,3-butandiol, and the selectivity of acetoin to organic acids were investigated and compared at different concentrations of ethanolammonium butyrate (EOAB) and K 3 PO 4 . In a SOE system consisted of 6% EOAB-38% K 3 PO 4 (w/w), the recovery of acetoin, IL and 2,3-butandiol was 92.7%, 76.0% and 86.0%, respectively, and the selectivity of acetoin to lactic acid and acetic acid was 16.46 and 3.85, respectively. The ATR-IR spectra showed the hydrogen bonds formed between acetoin and O-H, N-H, –COO – of hydroxylammonium IL played an important role in the efficient extraction of acetoin from fermentation broths.

CAS / MDL: 513-86-0 7778-53-2
研究领域: 生物化工 · 化学工程
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BIOCHEMICAL ENGINEERING JOURNAL · 2024 · IF 3.7

ORP-Regulated Natural Accumulation of Pyruvate in Actinobacillus succinogenes 130Z

Ying Li,Yu Zeng,Shuo Zhao,Zhen Wang,Li Chen,Kequan Chen

Pyruvate, a pivotal metabolite in the glycolytic pathway, typically confronts substantial barriers to its natural accumulation within microbial cells. This study successfully facilitated the natural accumulation of pyruvate in Actinobacillus succinogenes 130Z by fine-tuning the oxidation-reduction potential (ORP) in the fermentation milieu. A mechanistic exploration revealed that the accumulation of pyruvate was optimized when ORP conditions favorably modulated pyruvate kinase activity and concurrently suppressed succinate dehydrogenase activity. By integrating the influence of metal ions on enzymatic functions with an innovative aluminum ion-mediated ORP control strategy, we achieved a pyruvate yield of 27.54   g/L over 20   hours, which constitutes an 89.54% increase compared to the baseline. Additionally, the production rate of pyruvate reached 1.38   g/L·h. This investigation not only elucidates the metabolic underpinnings that facilitate the natural enrichment of glycolytic intermediates in Actinobacillus succinogenes 130Z but also lays a robust theoretical foundation for the industrial-scale fermentation of pyruvate. Moreover, the capability to efficiently and rapidly concentrate essential platform metabolites within the glycolytic pathway is of paramount significance, potentially propelling forward the research and synthesis of various downstream metabolic products.

研究领域: 微生物学 · 生物化学 · 工业发酵
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Journal of Environmental Chemical Engineering · 2025 · IF 7.2

Efficient synergistic enhancing degradation of waste poly(ethylene terephthalate) by combination of DBU with zinc 2-ethylhexanoate

Lu Li,Sihong Xu,Liang Jin,Wenxing Chen,Shichang Chen

It is essential to find a depolymerization system with good catalytic activity, easy operation, and high efficiency for the degradation of waste PET. The synergistic catalytic effect of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and zinc 2-ethylhexanoate (ZnEH) in PET glycolysis was investigated. Waste PET can be more efficient when completely degraded than single organocatalyst or zinc salt or previous DBU/Zn(OAc) 2 , and the yield of BHET reaches 84.1 % under optimal reaction conditions with the molar ratio of 2:1 of DBU to ZnEH and the weight ratio of 3:1 of EG to PET, the temperature of 180 °C and at 60 minutes. By combining experimental results with density functional theory (DFT) calculations, the synergistic enhancing degradation mechanism that generates hydrogen and coordination bonds is proposed. The purified depolymerization product of BHET was repolymerized to PET, delightfully the r-PET was almost identical to virgin PET.

研究领域: 材料科学 · 环境科学 · 化学工程
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APPLIED AND ENVIRONMENTAL MICROBIOLOGY · 2020 ·Vol. 86 ·期 19 · IF 4.016

3-Hydroxypyridine Dehydrogenase HpdA Is Encoded by a Novel Four-Component Gene Cluster and Catalyzes the First Step of 3-Hydroxypyridine Catabolism in Ensifer adhaerens HP1

Haixia Wang,Xiaoyu Wang,Hao Ren,Xuejun Wang,Zhenmei Lu

3-Hydroxypyridine (3HP) is an important natural pyridine derivative. Ensifer adhaerens HP1 can utilize 3HP as its sole sources of carbon, nitrogen, and energy to grow, but the genes responsible for the degradation of 3HP remain unknown. In this study, we predicted that a gene cluster, designated 3hpd, might be responsible for the degradation of 3HP. The analysis showed that the initial hydroxylation of 3HP in E. adhaerens HP1 was catalyzed by a four-component dehydrogenase (HpdA1A2A3A4) and led to the formation of 2,5-dihydroxypyridine (2,5-DHP). In addition, the SRPBCC component in HpdA existed as a separate subunit, which is different from other SRPBCC-containing molybdohydroxylases acting on N-heterocyclic aromatic compounds. Moreover, the results demonstrated that the phosphoenolpyruvate (PEP)-utilizing protein and pyruvate-phosphate dikinase were involved in the HpdA activity, and the presence of the gene cluster 3hpd was discovered in the genomes of diverse microbial strains. Our findings provide a better understanding of the microbial degradation of pyridine derivatives in nature and indicated that further research on the origin of the discovered four-component dehydrogenase with a separate SRPBCC domain and the function of PEP-utilizing protein and pyruvate-phosphate dikinase might be of great significance.IMPORTANCE 3-Hydroxypyridine is an important building block for the synthesis of drugs, herbicides, and antibiotics. Although the microbial degradation of 3-hydroxypyridine has been studied for many years, the molecular mechanisms remain unclear. Here, we show that 3hpd is responsible for the catabolism of 3-hydroxypyridine. The 3hpd gene cluster was found to be widespread in Actinobacteria, Rubrobacteria, Thermoleophilia, and Alpha-, Beta-, and Gammaproteobacteria, and the genetic organization of the 3hpd gene clusters in these bacteria shows high diversity. Our findings provide new insight into the catabolism of 3-hydroxypyridine in bacteria.

CAS / MDL: 5154-01-8
研究领域: 微生物学 · 生物化学 · 分子生物学 · 环境科学
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ChemistrySelect · 2022 ·Vol. 7 ·期 27 ·e202201140 · IF 2.307

Investigation and Separation of Chromogenic Substances in Glyoxylic Acid Generated by Electrochemical Reduction of Oxalic Acid

Xiyang Wang,Siraj Ullah,Shuozhen Hu,Xinsheng Zhang

Graphical The composition of chromogenic impurities in the glyoxylic acid prepared by electroreduction of oxalic acid is studied. The chromogenic impurities are mainly composed of glyceric acid and pyruvic acid. 92.97 % of the chromatic substances can be removed from glyoxylic acid via electrodialysis. Oxalic acid is also separated from glyoxylic acid by electrodialysis method. Electroreduction of oxalic acid (OA) is an effective process to produce glyoxylic acid (GA). However, electrochemically generated GA solution is yellow, which lowers the quality of GA and affects the application in producing the downstream products. It is urgent to investigate the composition of chromogenic substances (CSs) and separate them from the GA solution. In this work, the presence of tartaric acid, glyceric acid, and pyruvic acid in the electrochemically generated GA solution is successfully confirmed by high-performance liquid chromatography-electrospray-mass spectrometry. Tartaric acid is originally generated from GA and glycolic acid, and then further reduced to obtain chromogenic glyceric acid and pyruvic acid. 92.97 % of CSs could be successfully removed from the GA solution by electrodialysis at 240.64 A/m 2 and 25 °C. A separation of OA and GA is also achieved by electrodialysis. This study makes a significant contribution to the industrialization of electroreduction process to prepare GA.

研究领域: 化学工程 · 环境科学 · 工业化学
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Environmental Chemistry and Ecotoxicology · 2025 · IF 8.2

6-PPD quinone at environmentally relevant concentrations disrupts citric acid cycle in Caenorhabditis elegans: Role of reduction in acetyl CoA and pyruvate contents

Xin Wan,Geyu Liang,Dayong Wang

The 6-PPD quinone (6-PPDQ) is derived from 6-PPD, an antioxidant added in tires. Citric acid cycle plays a pivotal role in biochemical metabolisms. In Caenorhabditis elegans , we examined effect of 6-PPDQ exposure on citric acid cycle and the role of alteration in acetyl CoA and pyruvate contents during this process. In citric acid cycle, contents of intermediates were reduced by 0.1–10 μg/L 6-PPDQ. Meanwhile, expression of key enzyme genes ( cts-1 , idh-2 , dlst-1 , and dld-1 ) for citric acid cycle was decreased by 0.1–10 μg/L 6-PPDQ. After 6-PPDQ exposure, citric acid content was reduced by cts-1 RNAi, and NADH content was reduced by idh-2 , dlst-1 , and dld-1 RNAi. Exposure to 6-PPDQ (0.1–10 μg/L) further decreased acetyl CoA and pyruvate contents, and inhibited expression of enzyme genes ( dlat-1 and dld-1 ) governing acetyl CoA synthesis and enzyme genes ( pyk-1 and pyk-2 ) governing pyruvate synthesis. After 6-PPDQ exposure, dlat-1 and dld-1 RNAi reduced contents of acetyl CoA, citric acid, and NADH, and pyk-1 and pyk-2 RNAi reduced contents of pyruvate, citric acid, and NADH. In 6-PPDQ exposed nematodes, cts-1 , idh-2 , dlst-1 , dld-1 , dlat-1 , pyk-1 , and pyk-2 RNAi further caused susceptibility to 6-PPDQ toxicity. Our results suggested 6-PPDQ exposure risk in resulting in damage on citric acid cycle, which was linked to its toxicity induction.

CAS / MDL: 113-24-6
研究领域: 环境毒理学 · 分子生物学
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ACS Sustainable Chemistry & Engineering · 2024 · IF 7.1

One-Step Synthesis of PtPb Alloy Nanoparticles Via Wet Chemical Method for the Upgraded Recycling of PLA Plastic

Wenlong Pang,Bin Li,Yufeng Wu,Yu Zhang,Jun Yang,Zhongxun Tian,Shaonan Tian,Jianjun Li

Biodegradable plastics such as polylactic acid (PLA) have been extensively applied in numerous fields. Although PLA is degradable in natural environments, its decomposition postdisposal leads to resource wastage. Herein, we first employ enzymatic hydrolysis to degrade PLA. Subsequently, PtPb alloy nanoparticles are synthesized in a single step via a wet chemical method, catalyzing the reformation of the PLA enzymatic hydrolysis products into higher-value chemicals (pyruvic acid). Under conditions of an oxygen flow rate of 60 mL/min, a reaction temperature of 90 °C, and a reaction duration of 60 min, the conversion rate of lactic acid catalytic oxidative dehydrogenation to pyruvic acid reaches an impressive 96.86%, with a selectivity of 95.69%. Moreover, this catalyst exhibits satisfactory stability. Experimental and density functional theory (DFT) calculations are combined to ascertain the active state changes of PtPb and the reaction pathways for the catalytic oxidative dehydrogenation of lactic acid to pyruvic acid, as well as the free energy changes of different catalysts in this transformation. In this work, we employ a simple synthetic strategy to specifically investigate the impact of PtPb alloy nanoparticles under various conditions on the catalytic oxidative dehydrogenation of lactic acid to pyruvic acid, offering a new research avenue for the waste treatment and resource utilization of biodegradable plastics in the future.

研究领域: 材料科学 · 环境科学 · 催化化学
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